Jullien D, Heydrick S J, Gautier N, Van Obberghen E, Le Marchand-Brustel Y
Institut National de la Santé et de la Recherche Médicale, Faculty ofMedicine, Nice, France.
Diabetes. 1996 Jul;45(7):869-75. doi: 10.2337/diab.45.7.869.
Insulin and IGF-I induced a similar stimulation of glucose transport in isolated soleus muscle. These actions require phosphatidylinositol (PI) 3-kinase activation since the PI 3-kinase inhibitor, wortmannin, blocked the stimulation by both peptides. We compared IGF-I with insulin in the ability to activate PI 3-kinase in the isolated soleus muscle from lean and gold thioglucose-induced obese insulin-resistant mice. In muscles from lean mice, IGF-I and insulin were able to activate PI 3-kinase with a similar time course, the effects being maximal within 3-5 min of stimulation. However, the IGF-I concentrations required to obtain similar effects on PI 3-kinase were about 10 times higher than the corresponding insulin doses. To determine through which receptor IGF-I was activating PI 3-kinase, the ability of IGF-I to activate both its own receptor and insulin receptor was simultaneously measured. Whatever the dose used (100 or 500 nmol/l), IGF-I activated to a nearly similar extent both the tyrosine kinase activity of its own receptor and that of the insulin receptor, suggesting that IGF-I was not only activating its receptor but was also able to stimulate the insulin receptor kinase. In muscles of obese insulin-resistant mice, although the defect of PI 3-kinase activation in response to IGF-I was relatively less pronounced (45%) than in response to insulin (70%) when compared with lean mice, PI 3-kinase stimulation was still markedly altered in response to IGF-I.
胰岛素和胰岛素样生长因子-I（IGF-I）对离体比目鱼肌葡萄糖转运的刺激作用相似。这些作用需要磷脂酰肌醇（PI）3-激酶激活，因为PI 3-激酶抑制剂渥曼青霉素可阻断这两种肽的刺激作用。我们比较了IGF-I和胰岛素在激活来自正常小鼠以及金硫葡萄糖诱导的肥胖胰岛素抵抗小鼠的离体比目鱼肌中PI 3-激酶的能力。在正常小鼠的肌肉中，IGF-I和胰岛素能够在相似的时间进程中激活PI 3-激酶，刺激3 - 5分钟时作用达到最大。然而，获得对PI 3-激酶相似作用所需的IGF-I浓度比相应胰岛素剂量高约10倍。为了确定IGF-I通过哪种受体激活PI 3-激酶，同时测量了IGF-I激活其自身受体和胰岛素受体的能力。无论使用何种剂量（100或500 nmol/l），IGF-I对其自身受体酪氨酸激酶活性和胰岛素受体酪氨酸激酶活性的激活程度几乎相似，这表明IGF-I不仅激活其自身受体，还能够刺激胰岛素受体激酶。在肥胖胰岛素抵抗小鼠的肌肉中，与正常小鼠相比，尽管IGF-I诱导的PI 3-激酶激活缺陷（45%）相对于胰岛素诱导的（70%）相对不那么明显，但IGF-I诱导的PI 3-激酶刺激仍有明显改变。
